Cytokine Influence on Killing of Fresh Chronic Lymphocytic Leukemia Cells by Human Leukocytes
The feasibility of combining the Lym-1 monoclonal antibody (MoAb) with interferon-γ(IFN-γ) in the treatment of chronic lymphocytic leukemia (CLL) was evaluated. We used an in vitro tumor lysis model that incorporated fresh CLL cells from 21 different patients as targets for two distinct normal human...
Gespeichert in:
Veröffentlicht in: | Blood 1991-06, Vol.77 (12), p.2707-2715 |
---|---|
Hauptverfasser: | , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 2715 |
---|---|
container_issue | 12 |
container_start_page | 2707 |
container_title | Blood |
container_volume | 77 |
creator | Ćemerlíc, Dževad Dadey, Barbara Han, Tin Vaickus, Louis |
description | The feasibility of combining the Lym-1 monoclonal antibody (MoAb) with interferon-γ(IFN-γ) in the treatment of chronic lymphocytic leukemia (CLL) was evaluated. We used an in vitro tumor lysis model that incorporated fresh CLL cells from 21 different patients as targets for two distinct normal human leukocyte effector subsets, neutrophils, and peripheral blood mononuclear cells (PBMCs). Lym-1 antigen (Lym-1- Ag) expression varied greatly and did not correlate with the expression of other CLL-associated antigens such as CD5, CD19, or HLA-DR. CLL cells were not lysed by neutrophils alone or with IFN-γ in the absence of Lym-1. Neutrophil Lym-1-dependent cytotoxicity (ADCC) in the absence of IFN-γ was weak and inconsistent. IFN-γ exposure induced MoAb-dependent lysis of 80% of 21 CLL targets and resulted in an eightfold augmentation of neutrophil ADCC against the remainder. Cytotoxicity correlated directly and positively with Lym-1-Ag expression. Confirmation of the need for interaction between neutrophil IgG Fc receptors (FcγRs) and the Fc portion of the Lym-1 MoAb was obtained by demonstrating that purified Staphylococcus aureus Protein A (SpA) inhibited ADCC. IFN-γ exposure caused no consistent alterations in Lym-1-Ag expression on CLL cells so that target antigen upregulation was unlikely to account for augmentation of neutrophil ADCC. PBMCs alone, exposed to interkeukin-2 (IL-2) or IFN-γ,or with Lym-1 in the presence or absence of IL-2 or IFN-γ were unable to lyse CLL targets. PBMCs were able to kill Raji Burkitt lymphoma cells in conjunction with Lym-1, so their ability to interact with Lym-1-coated targets and their lytic functions appeared intact. These results emphasize the importance of examining fresh tumor cells with different leukocyte effector subsets before designing a clinical trial that combines a therapeutic MoAb with a cytokine.©1991 by The American Society of Hematology. |
doi_str_mv | 10.1182/blood.V77.12.2707.2707 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_80606089</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497120852902</els_id><sourcerecordid>80606089</sourcerecordid><originalsourceid>FETCH-LOGICAL-c440t-b52c4b92ed033c61063cf9dd77a933e64d49a91cc7bbf6efef56c84cdfca30813</originalsourceid><addsrcrecordid>eNqFkFuL1DAUgIO4rLOrP0HJg_jWMbde8qYU94ID-6K-SUiTEydum4xJK_TfbzszrI8SOAk537nwIfSOki2lDfvY9THa7Y-63lK2ZTWpj-EF2tCSNQUhjLxEG0JIVQhZ01foKuffhFDBWXmJLqkkgjXlBv1s5zE--gD4Prh-gmAAx4C_-r734ReODt8kyHvc7lMM3uDdPBz20czj-obpEQavcQt9n3E347tp0OH4vyKQX6MLp_sMb873Nfp-8-Vbe1fsHm7v28-7wghBxqIrmRGdZGAJ56aipOLGSWvrWkvOoRJWSC2pMXXXuQocuLIyjTDWGc1JQ_k1-nDqe0jxzwR5VIPPZtlKB4hTVg2pltPIBaxOoEkx5wROHZIfdJoVJWr1qo5e1eJVUaZWpcewFL49T5i6Aey_spPIJf_-nNfZ6N4lHYzPz5gQvBRynf_phMFi46-HpLLxq3TrE5hR2ej_t8kTLZuYtg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>80606089</pqid></control><display><type>article</type><title>Cytokine Influence on Killing of Fresh Chronic Lymphocytic Leukemia Cells by Human Leukocytes</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Ćemerlíc, Dževad ; Dadey, Barbara ; Han, Tin ; Vaickus, Louis</creator><creatorcontrib>Ćemerlíc, Dževad ; Dadey, Barbara ; Han, Tin ; Vaickus, Louis</creatorcontrib><description>The feasibility of combining the Lym-1 monoclonal antibody (MoAb) with interferon-γ(IFN-γ) in the treatment of chronic lymphocytic leukemia (CLL) was evaluated. We used an in vitro tumor lysis model that incorporated fresh CLL cells from 21 different patients as targets for two distinct normal human leukocyte effector subsets, neutrophils, and peripheral blood mononuclear cells (PBMCs). Lym-1 antigen (Lym-1- Ag) expression varied greatly and did not correlate with the expression of other CLL-associated antigens such as CD5, CD19, or HLA-DR. CLL cells were not lysed by neutrophils alone or with IFN-γ in the absence of Lym-1. Neutrophil Lym-1-dependent cytotoxicity (ADCC) in the absence of IFN-γ was weak and inconsistent. IFN-γ exposure induced MoAb-dependent lysis of 80% of 21 CLL targets and resulted in an eightfold augmentation of neutrophil ADCC against the remainder. Cytotoxicity correlated directly and positively with Lym-1-Ag expression. Confirmation of the need for interaction between neutrophil IgG Fc receptors (FcγRs) and the Fc portion of the Lym-1 MoAb was obtained by demonstrating that purified Staphylococcus aureus Protein A (SpA) inhibited ADCC. IFN-γ exposure caused no consistent alterations in Lym-1-Ag expression on CLL cells so that target antigen upregulation was unlikely to account for augmentation of neutrophil ADCC. PBMCs alone, exposed to interkeukin-2 (IL-2) or IFN-γ,or with Lym-1 in the presence or absence of IL-2 or IFN-γ were unable to lyse CLL targets. PBMCs were able to kill Raji Burkitt lymphoma cells in conjunction with Lym-1, so their ability to interact with Lym-1-coated targets and their lytic functions appeared intact. These results emphasize the importance of examining fresh tumor cells with different leukocyte effector subsets before designing a clinical trial that combines a therapeutic MoAb with a cytokine.©1991 by The American Society of Hematology.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.V77.12.2707.2707</identifier><identifier>PMID: 1904285</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Antibodies, Monoclonal - immunology ; Antibody-Dependent Cell Cytotoxicity ; Biological and medical sciences ; Cytotoxicity, Immunologic ; Female ; Hematologic and hematopoietic diseases ; Humans ; Immunophenotyping ; Interferon-gamma - pharmacology ; Interleukin-2 - pharmacology ; Leukemia, Lymphocytic, Chronic, B-Cell - immunology ; Leukocytes, Mononuclear - immunology ; Male ; Medical sciences ; Neutrophils - immunology ; Recombinant Proteins ; Tumor Cells, Cultured</subject><ispartof>Blood, 1991-06, Vol.77 (12), p.2707-2715</ispartof><rights>1991 American Society of Hematology</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-b52c4b92ed033c61063cf9dd77a933e64d49a91cc7bbf6efef56c84cdfca30813</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4435499$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1904285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ćemerlíc, Dževad</creatorcontrib><creatorcontrib>Dadey, Barbara</creatorcontrib><creatorcontrib>Han, Tin</creatorcontrib><creatorcontrib>Vaickus, Louis</creatorcontrib><title>Cytokine Influence on Killing of Fresh Chronic Lymphocytic Leukemia Cells by Human Leukocytes</title><title>Blood</title><addtitle>Blood</addtitle><description>The feasibility of combining the Lym-1 monoclonal antibody (MoAb) with interferon-γ(IFN-γ) in the treatment of chronic lymphocytic leukemia (CLL) was evaluated. We used an in vitro tumor lysis model that incorporated fresh CLL cells from 21 different patients as targets for two distinct normal human leukocyte effector subsets, neutrophils, and peripheral blood mononuclear cells (PBMCs). Lym-1 antigen (Lym-1- Ag) expression varied greatly and did not correlate with the expression of other CLL-associated antigens such as CD5, CD19, or HLA-DR. CLL cells were not lysed by neutrophils alone or with IFN-γ in the absence of Lym-1. Neutrophil Lym-1-dependent cytotoxicity (ADCC) in the absence of IFN-γ was weak and inconsistent. IFN-γ exposure induced MoAb-dependent lysis of 80% of 21 CLL targets and resulted in an eightfold augmentation of neutrophil ADCC against the remainder. Cytotoxicity correlated directly and positively with Lym-1-Ag expression. Confirmation of the need for interaction between neutrophil IgG Fc receptors (FcγRs) and the Fc portion of the Lym-1 MoAb was obtained by demonstrating that purified Staphylococcus aureus Protein A (SpA) inhibited ADCC. IFN-γ exposure caused no consistent alterations in Lym-1-Ag expression on CLL cells so that target antigen upregulation was unlikely to account for augmentation of neutrophil ADCC. PBMCs alone, exposed to interkeukin-2 (IL-2) or IFN-γ,or with Lym-1 in the presence or absence of IL-2 or IFN-γ were unable to lyse CLL targets. PBMCs were able to kill Raji Burkitt lymphoma cells in conjunction with Lym-1, so their ability to interact with Lym-1-coated targets and their lytic functions appeared intact. These results emphasize the importance of examining fresh tumor cells with different leukocyte effector subsets before designing a clinical trial that combines a therapeutic MoAb with a cytokine.©1991 by The American Society of Hematology.</description><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibody-Dependent Cell Cytotoxicity</subject><subject>Biological and medical sciences</subject><subject>Cytotoxicity, Immunologic</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Interferon-gamma - pharmacology</subject><subject>Interleukin-2 - pharmacology</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neutrophils - immunology</subject><subject>Recombinant Proteins</subject><subject>Tumor Cells, Cultured</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkFuL1DAUgIO4rLOrP0HJg_jWMbde8qYU94ID-6K-SUiTEydum4xJK_TfbzszrI8SOAk537nwIfSOki2lDfvY9THa7Y-63lK2ZTWpj-EF2tCSNQUhjLxEG0JIVQhZ01foKuffhFDBWXmJLqkkgjXlBv1s5zE--gD4Prh-gmAAx4C_-r734ReODt8kyHvc7lMM3uDdPBz20czj-obpEQavcQt9n3E347tp0OH4vyKQX6MLp_sMb873Nfp-8-Vbe1fsHm7v28-7wghBxqIrmRGdZGAJ56aipOLGSWvrWkvOoRJWSC2pMXXXuQocuLIyjTDWGc1JQ_k1-nDqe0jxzwR5VIPPZtlKB4hTVg2pltPIBaxOoEkx5wROHZIfdJoVJWr1qo5e1eJVUaZWpcewFL49T5i6Aey_spPIJf_-nNfZ6N4lHYzPz5gQvBRynf_phMFi46-HpLLxq3TrE5hR2ej_t8kTLZuYtg</recordid><startdate>19910615</startdate><enddate>19910615</enddate><creator>Ćemerlíc, Dževad</creator><creator>Dadey, Barbara</creator><creator>Han, Tin</creator><creator>Vaickus, Louis</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19910615</creationdate><title>Cytokine Influence on Killing of Fresh Chronic Lymphocytic Leukemia Cells by Human Leukocytes</title><author>Ćemerlíc, Dževad ; Dadey, Barbara ; Han, Tin ; Vaickus, Louis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-b52c4b92ed033c61063cf9dd77a933e64d49a91cc7bbf6efef56c84cdfca30813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibody-Dependent Cell Cytotoxicity</topic><topic>Biological and medical sciences</topic><topic>Cytotoxicity, Immunologic</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Interferon-gamma - pharmacology</topic><topic>Interleukin-2 - pharmacology</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neutrophils - immunology</topic><topic>Recombinant Proteins</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ćemerlíc, Dževad</creatorcontrib><creatorcontrib>Dadey, Barbara</creatorcontrib><creatorcontrib>Han, Tin</creatorcontrib><creatorcontrib>Vaickus, Louis</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ćemerlíc, Dževad</au><au>Dadey, Barbara</au><au>Han, Tin</au><au>Vaickus, Louis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytokine Influence on Killing of Fresh Chronic Lymphocytic Leukemia Cells by Human Leukocytes</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>1991-06-15</date><risdate>1991</risdate><volume>77</volume><issue>12</issue><spage>2707</spage><epage>2715</epage><pages>2707-2715</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>The feasibility of combining the Lym-1 monoclonal antibody (MoAb) with interferon-γ(IFN-γ) in the treatment of chronic lymphocytic leukemia (CLL) was evaluated. We used an in vitro tumor lysis model that incorporated fresh CLL cells from 21 different patients as targets for two distinct normal human leukocyte effector subsets, neutrophils, and peripheral blood mononuclear cells (PBMCs). Lym-1 antigen (Lym-1- Ag) expression varied greatly and did not correlate with the expression of other CLL-associated antigens such as CD5, CD19, or HLA-DR. CLL cells were not lysed by neutrophils alone or with IFN-γ in the absence of Lym-1. Neutrophil Lym-1-dependent cytotoxicity (ADCC) in the absence of IFN-γ was weak and inconsistent. IFN-γ exposure induced MoAb-dependent lysis of 80% of 21 CLL targets and resulted in an eightfold augmentation of neutrophil ADCC against the remainder. Cytotoxicity correlated directly and positively with Lym-1-Ag expression. Confirmation of the need for interaction between neutrophil IgG Fc receptors (FcγRs) and the Fc portion of the Lym-1 MoAb was obtained by demonstrating that purified Staphylococcus aureus Protein A (SpA) inhibited ADCC. IFN-γ exposure caused no consistent alterations in Lym-1-Ag expression on CLL cells so that target antigen upregulation was unlikely to account for augmentation of neutrophil ADCC. PBMCs alone, exposed to interkeukin-2 (IL-2) or IFN-γ,or with Lym-1 in the presence or absence of IL-2 or IFN-γ were unable to lyse CLL targets. PBMCs were able to kill Raji Burkitt lymphoma cells in conjunction with Lym-1, so their ability to interact with Lym-1-coated targets and their lytic functions appeared intact. These results emphasize the importance of examining fresh tumor cells with different leukocyte effector subsets before designing a clinical trial that combines a therapeutic MoAb with a cytokine.©1991 by The American Society of Hematology.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>1904285</pmid><doi>10.1182/blood.V77.12.2707.2707</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0006-4971 |
ispartof | Blood, 1991-06, Vol.77 (12), p.2707-2715 |
issn | 0006-4971 1528-0020 |
language | eng |
recordid | cdi_proquest_miscellaneous_80606089 |
source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Antibodies, Monoclonal - immunology Antibody-Dependent Cell Cytotoxicity Biological and medical sciences Cytotoxicity, Immunologic Female Hematologic and hematopoietic diseases Humans Immunophenotyping Interferon-gamma - pharmacology Interleukin-2 - pharmacology Leukemia, Lymphocytic, Chronic, B-Cell - immunology Leukocytes, Mononuclear - immunology Male Medical sciences Neutrophils - immunology Recombinant Proteins Tumor Cells, Cultured |
title | Cytokine Influence on Killing of Fresh Chronic Lymphocytic Leukemia Cells by Human Leukocytes |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T20%3A11%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cytokine%20Influence%20on%20Killing%20of%20Fresh%20Chronic%20Lymphocytic%20Leukemia%20Cells%20by%20Human%20Leukocytes&rft.jtitle=Blood&rft.au=%C4%86emerl%C3%ADc,%20D%C5%BEevad&rft.date=1991-06-15&rft.volume=77&rft.issue=12&rft.spage=2707&rft.epage=2715&rft.pages=2707-2715&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood.V77.12.2707.2707&rft_dat=%3Cproquest_cross%3E80606089%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=80606089&rft_id=info:pmid/1904285&rft_els_id=S0006497120852902&rfr_iscdi=true |